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Paper Chase

A microengineered vascularized bleeding model that integrates the principal components of hemostasis.

Nat Commun. Feb 06, 2018;9(1):509.
Sakurai Y, Hardy ET, Ahn B, Tran R, Fay ME, Ciciliano JC, Mannino RG, Myers DR, Qiu Y, Carden MA, Baldwin WH, Meeks SL, Gilbert GE, Jobe SM, Lam WA.

Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA. wilbur.lam@emory.edu.

Abstract:

Hemostasis encompasses an ensemble of interactions among platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces, but current assays assess only isolated aspects of this complex process. Accordingly, here we develop a comprehensive in vitro mechanical injury bleeding model comprising an "endothelialized" microfluidic system coupled with a microengineered pneumatic valve that induces a vascular "injury". With perfusion of whole blood, hemostatic plug formation is visualized and "in vitro bleeding time" is measured. We investigate the interaction of different components of hemostasis, gaining insight into several unresolved hematologic issues. Specifically, we visualize and quantitatively demonstrate: the effect of anti-platelet agent on clot contraction and hemostatic plug formation, that von Willebrand factor is essential for hemostasis at high shear, that hemophilia A blood confers unstable hemostatic plug formation and altered fibrin architecture, and the importance of endothelial phosphatidylserine in hemostasis. These results establish the versatility and clinical utility of our microfluidic bleeding model.

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